The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust.

Background: Lung metastasectomy in the treatment of advanced colorectal cancer has been widely adopted without good evidence of survival or palliative benefit. We aimed to test its effectiveness in a randomised controlled trial (RCT).Methods: Multidisciplinary teams in 13 hospitals recruited participants with potentially resectable lung metastases to a multicentre, two-arm RCT comparing active monitoring with or without metastasectomy. Other local or systemic treatments were decided by the local team. Randomisation was remote and stratified by site with minimisation for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, the number of metastases, and carcinoembryonic antigen level. The central Trial Management Group were blind to patient allocation until completion of the analysis. Analysis was on intention to treat with a margin for non-inferiority of 10%.Results: Between December 2010 and December 2016, 65 participants were randomised. Characteristics were well-matched in the two arms and similar to those in reported studies: age 35 to 86 years (interquartile range (IQR) 60 to 74); primary resection IQR 16 to 35 months previously; stage at resection T1, 2 or 3 in 3, 8 and 46; N1 or N2 in 31 and 26; unknown in 8. Lung metastases 1 to 5 (median 2); 16/65 had previous liver metastases; carcinoembryonic antigen normal in 55/65. There were no other interventions in the first 6 months, no crossovers from control to treatment, and no treatment-related deaths or major adverse events. The Hazard ratio for death within 5 years, comparing metastasectomy with control, was 0.82 (95%CI 0.43, 1.56).Conclusions: Because of poor and worsening recruitment, the study was stopped. The small number of participants in the trial (N = 65) precludes a conclusive answer to the research question given the large overlap in the confidence intervals in the proportions still alive at all time points. A widely held belief is that the 5-year absolute survival benefit with metastasectomy is about 35%: 40% after metastasectomy compared to < 5% in controls. The estimated survival in this study was 38% (23–62%) for metastasectomy patients and 29% (16–52%) in the well-matched controls. That is the new and important finding of this RCT.Trial registration: ClinicalTrials.gov, ID:NCT01106261. Registered on 19 April 2010

Aim: Lung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5‐year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial.Method: Multidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two‐arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention‐to‐treat analysis.Results: From 2010 to 2016, 93 participants were randomized. These patients were 35–86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1–6.6) years compared with 3.8 (95% CI: 3.1–4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56–1.56). Use of chemotherapy or local ablation was infrequent and similar in each group.Conclusion: Patients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single‐arm follow‐up studies. The groups were well matched with features similar to those reported in case series.

Pulmonary metastasectomy is a commonly performed operation and is tending to increase as part of a concept of personalised treatment for advanced cancer. There have been no randomised trials; belief in effectiveness of metastasectomy is based on registry data and surgical follow-up studies. These retrospective series are comprised predominately of solitary or few metastases with primary resection to metastasectomy intervals longer than 2–3 years. Five-year survival rates of 30–50% are recorded, but as case selection is based on favourable prognostic features, an apparent association between metastasectomy and survival cannot be interpreted as causation. Cancers for which lung metastasectomy is used are considered in four pathological groups. In non-seminomatous germ cell tumour, for which chemotherapy is highly effective, excision of residual pulmonary disease guides future treatment and in particular allows an informed decisions as to further chemotherapy. Sarcoma metastasises predominately to lung and pulmonary metastasectomy for both bone and soft tissues sarcoma is routinely considered as a treatment option but without randomised data. The commonest circumstance for lung and liver metastasectomy is colorectal cancer. Repeated resections and ablations are commonplace but without evidence of effectiveness for either. For melanoma, results are particularly poor, but lung metastases are resected when no other treatment options are available. In this review, the available evidence is considered and the conclusion reached is that in the absence of randomised trials there is uncertainty about effectiveness. A randomised controlled trial, Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), is in progress and randomised trials in sarcoma seem warranted.

Summary Objectives: Surgical removal of pulmonary metastases from colorectal cancer is undertaken increasingly but the practice is variable. There have been no randomized trials of effectiveness. We needed evidence from a systematic review to plan a randomized controlled trial. Design: A formal search for all studies concerning the practice of pulmonary metastasectomy was undertaken including all published articles using pre-specified keywords. Abstracts were screened, reviewed and data extracted by at least two of the authors. Information across studies was collated in a quantitative synthesis. Results: Of 101 articles identified, 51 contained sufficient quantitative information to be included in the synthesis. The reports were published between 1971 and 2007, and reported on 3504 patients. There was little change over time in patient characteristics such as age, sex, the time elapsed since resection of the primary cancer, its site or stage. The proportion with multiple metastases or elevated carcinoma embryonic antigen (CEA) did not change over time but there was an apparent increase in the proportion of patients who also had hepatic metastasectomy. Differences in 5-year survival between groups defined by CEA or by single versus multiple metastases persisted over time. Few data were available concerning postoperative morbidity, postoperative lung function or change in symptoms. Conclusion: The quality of evidence available concerning pulmonary metastasectomy in colorectal cancer is not sufficient to draw inferences concerning the effectiveness of this surgery. There is great variety in what was reported and its utility. Given the burdensome nature of the surgery involved, better evidence, ideally in the form of a randomized trial, is required for the continuance of this practice.

Objectives Sarcoma has a predilection to metastasis to the lungs. Surgical excision of these metastases (pulmonary metastasectomy) when possible has become standard practice. We reviewed the published selection and outcome data. Design Systematic review of published reports that include survival rates or any other outcome data. Survival data were put in the context of those in a cancer registry. Setting Specialist thoracic surgical centres reporting the selection and outcome for pulmonary metastasectomy in 18 follow-up studies published 1991–2010. Participants Patients having one or more of 1357 pulmonary metastasectomy operations performed between 1980 and 2006. Interventions All patients had surgical pulmonary metastasectomy. A first operation was reported in 1196 patients. Of 1357 patients, 43% had subsequent metastasectomy, some having 10 or more thoracotomies. Three studies were confined to patients having repeated pulmonary metastasectomy. Primary and secondary outcome measures Survival data to various time points usually 5 years and sometimes 3 or 10 years. No symptomatic or quality of life data were reported. Results About 34% and 25% of patients were alive 5 years after a first metastasectomy operation for bone or soft tissues sarcoma respectively. Better survival was reported with fewer metastases and longer intervals between diagnosis and the appearance of metastases. In the Thames Cancer Registry for 1985–1994 and 1995–2004 5 year survival rates for all patients with metastatic sarcoma were 20% and 25% for bone, and for soft tissue sarcoma 13% and 15%. Conclusions The 5 year survival rate among sarcoma patients who are selected to have pulmonary metastasectomy is higher than that observed among unselected registry data for patients with any metastatic disease at diagnosis. There is no evidence that survival difference is attributable to metastasectomy. No data were found on respiratory or any other symptomatic benefit. Given the certain harm associated with thoracotomy, often repeated, better evidence is required.